AS Patients Without Spinal Fusion Are a Distinct Subgroup

Syndesmophytes are not present in a subgroup of patients with ankylosing spondylitis (AS) and sacroiliac (SI) joint fusion who have had the disease for 20 years or longer, according to findings from a nested case-control study.

Syndesmophytes did not occur in only 23 (7%) of 354 patients, and these patients without spinal-fusing bone growths were less likely to be female but very likely to be HLA-B27 positive, Lauren K. Ridley, MD, a rheumatologist at the University of Texas Health Science Center at Houston, and colleagues reported in The Journal of Rheumatology.

“Women appear to have a different phenotype in AS; we found that they are less likely to form syndesmophytes despite fused SI joints with at least 20 years of disease duration. We do not understand the reasons behind these differences among the possibilities of genetic, hormonal, and bio-mechanical factors,” the authors wrote.

AS is a heterogenous disease that affects different people in various ways, Ridley noted. “Prior research has shown that and hasn’t really elucidated how different people manifest their disease. Previous research has shown that women tend to have more nonradiographic spondylitis,” Ridley said in an interview.

“This is still a very heterogenous disease. We don’t fully understand it, and we don’t know why some patients present with SI joint disease [and] no syndesmophytes, or some patients have the opposite. Truly, we do need to do more studies to find out why some patients behave differently and if there are ways we can try to alter that,” Ridley continued.

The researchers evaluated 354 patients from the Prospective Study of Outcomes in Ankylosing Spondylitis (PSOAS). Of these patients, 23 did not have syndesmophytes. Patients were selected if they had fused SI joints (bilateral grade 4 sacroiliac joint disease) and had a disease course lasting 20 years or more. The researchers identified risk factors for syndesmophytes using classification and regression trees (CART) analysis and then reassessed their validity with univariable logistic regression models.

All 23 patients who had no syndesmophytes were HLA-B27 positive, and all patients older than 45 years at symptom onset had syndesmophytes.

The results also highlighted age of disease onset as an important predictor of syndesmophytes in males. Syndesmophytes were less likely to be reported in males with a disease onset at 16 years or younger.

The presence of syndesmophytes was linked with an age older than 16 years at symptom onset (OR, 2.72; 95% confidence interval, 1.15-6.45), and syndesmophytes were less likely to occur among HLA-B27 positive individuals (P = .03).

Females were less likely than males to have syndesmophytes, as verified by univariable analysis (odds ratio, 0.17; 95% confidence interval, 0.07-0.41).

“There is likely a complex interplay of factors leading to differences in radiographic damage between the sacroiliac joints and the spine in AS, and it is interesting to consider if HLA-B27 may have more effect on sacroiliac joint damage than spinal damage,” the authors noted.

Some limitations of the study include the researchers’ choice to compare a subtype with overt spinal involvement and a subtype with limited spinal involvement when other criteria could have been used to separate cases, and their use of the modified Stoke Ankylosing Spondylitis Scoring System (mSaSSS) to examine radiographic changes over time, as the mSaSSS does not take into account radiographic variation in the zygaphophyseal joints and thoracic spine (and were not part of the dataset). Another limitation was the relatively small cohort size, the researchers noted.

“This was a small study, and further studies are needed to elucidate why AS disease may behave differently in this and other subgroups,” Ridley and colleagues concluded.

Expert Commentary

Researchers agree that spinal structural damage is a predictor of further damage in patients with radiographic AS, Marina Magrey, MD, the Roland W. Moskowitz Professor in Rheumatic Diseases at Case Western Reserve University, Cleveland, said in an interview. She pointed out that previous literature has shown that longer disease durations make it more likely that patients will have syndesmophytes.

Dr Marina Magrey

Previous research has also shown that there was an association between structural damage in the SI joints and the function and mobility of the spine. This observation was independent of the disease activity and prior structural damage in the spine, Magrey noted.

“This is a very complex disease with very diverse manifestations. Traditionally, it was thought to be a disease of men, but now we believe it is equally common between men and women. The burden is equal between men and women, and they need to be treated equally. Both of them need to be treated early on to prevent this radiographic damage,” she said.

Looking ahead, there need to be more translational studies looking for answers as to why there are phenotypic differences between men and women, as well as why men have spinal fusion more often than women. Bed-to-the-bench studies are warranted to get more answers, she said.

The study was supported by an NIH Centers for Translational Science Award grant. The researchers declared having no conflicts of interest related to the study. One author is supported by the National Institute of Arthritis and Musculoskeletal and Skin Diseases Intramural Research Program, and another by the Spondyloarthritis Association of America and the University of Texas Health Center for Clinical and Translational Sciences KL2 program. Another author is an adviser for AbbVie, Eli Lilly, Gilead, Janssen, MoonLake, Novartis, Pfizer, and UCB, and has grant support from Novartis, Pfizer, and UCB.

Magrey disclosed being a consultant for Novartis, UCB, Pfizer, AbbVie, Janssen, Bristol-Myers Squibb, and Eli Lilly.

This article originally appeared on, part of the Medscape Professional Network.

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